Although fine needle aspiration (FNA) cytology is the best diagnostic tool in the differential diagnosis of a thyroid nodule, it often cannot differentiate a benign from a malignant lesion. Consequently, a majority of patients with thyroid nodules require surgery because of a suspicious, but not definitive, diagnosis of malignancy. Because the surgical management for benign and malignant thyroid neoplasms differ, patients with suspicious FNAs may be treated in a less than ideal fashion surgically. Although others and we have documented various genetic alterations in thyroid neoplasms, no specific alteration(s) can reliably distinguish benign from malignant lesions. We propose that there are specific gene expression patterns associated with the various thyroid tumor types and that these differing expression patterns can be capitalized upon to differentiate one tumor type from another. We therefore propose to genotype the most common benign and malignant thyroid lesions that present as suspicious thyroid FNA samples by cDNA microarray analysis. To accomplish these goals we propose the following: Specific Aim 1: To evaluate pooled thyroid tumor samples from follicular adenomas and corresponding normal thyroid by comprehensive cDNA microarray analysis using nylon filter arrays containing 37,000 genes. We have evaluated papillary thyroid cancers with this approach. We propose the same for follicular adenomas. Specific Aim 2: To evaluate individual thyroid tumor samples from follicular adenomas and papillary thyroid cancers and corresponding normal thyroid using cDNA glass slide arrays. In concert with the analysis described under specific aim 1, data will be analyzed to discover consistent gene expression patterns in these tumors by cluster analysis. Specific Aim 3: To independently validate the results of the array analysis by measuring expression levels of selected genes individually. This will be performed using quantitative real-time RT-PCR on RNA samples from a panel of thyroid tumors.